Background Considerable studies have demonstrated that activation of spinal cord microglia plays a critical role in the modulation of neuronal functions. In addition, activated microglia affects the spinal processing of nociceptive signaling, and is also involved in the regulation of central sensitization, which underlying neural mechanism of neuropathic pain. Objective To explore the activation mechanism of spinal cord microglia in the development of neuropathic pain. Content This article reviewed the research advances in the mechanisms of spinal microglia activation. It focuses on the extracellular and intracellular signal transduction for microglia activation under neuropathic pain condition. Trend The role of microglia in neuropathic pain continues to be the focus of pain research. Studying the role and mechanisms of spinal cord microglia may lead to more effective management of neuropathic pain.